NeuroCognition After Carotid Recanalization: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for NeuroCognition After Carotid Recanalization (NCT04219774), a randomized phase 2 study. The primary outcome is Change in Montreal Cognitive Assessment (MoCA) Score.

2. Clinical Question

The study concerns people with symptomatic complete occlusion of the internal carotid artery attributed to atherosclerotic disease. The registry describes cognitive impairment as a concern in this population and frames the study as exploratory. Its main question is whether cognitive scores change over time among participants assigned to endovascular intervention compared with participants assigned to medical management. The primary measure is change in Montreal Cognitive Assessment (MoCA) score, assessed at baseline, 6 months, and 12 months.

The registry also describes a non-randomized observational arm. Those participants met all inclusion criteria except the abnormal CTP criterion and were eligible for best medical management only. Their status means they should not be treated as part of a randomized comparison. The registry record does not report primary-outcome results, so the direction, size, and precision of any between-group difference cannot be assessed from the record.

3. Trial Design

This is a completed phase 2 study registered as randomized, single-masked, and parallel-design, with enrollment of 25. The listed study dates are a start date of 2020-05-01 and a primary completion date of 2024-03-14. The sponsor is Duke University. The registry describes an endovascular arm and a medical arm, with eligible participants randomized to intervention or best medical management. The medical treatment is named as aspirin and clopidogrel, also described as maximal medical therapy.

A separate non-randomized observational arm is described. Participants in that arm met all inclusion criteria except abnormal CTP and could receive best medical management only. Because assignment to that arm was not randomized, its participants do not form a randomized treatment contrast with the endovascular arm. The registry record does not report how many participants were assigned to each arm or how many contributed primary-outcome data.

The record identifies the study as phase 2 and its background describes it as exploratory, with go/no-go criteria for proceeding to phase 3 based on generated data. Details of those criteria are not reported in the registry record. The identity of the masked party, allocation procedures, and the protocol’s full design rationale are not reported in the registry record. Although secondary outcomes include stroke within 30 days post procedure, intracranial hemorrhage within 72 hours post procedure, and deaths, results for these outcomes are not reported in the registry record. Completion status alone does not establish that outcome analyses or findings were posted.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Participants with data collected at both timepoints for each comparison.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Change in Montreal Cognitive Assessment (MoCA) Score, measured over Baseline, 6 months, 12 months.

The primary endpoint is change in Montreal Cognitive Assessment (MoCA) score. The MoCA is a screening tool used to assess cognitive function. Its possible score range is 0 to 30, and higher scores indicate better cognitive performance. A change score describes how an individual’s measured score differs between an assessment and a reference assessment; in this study, the stated assessment schedule includes baseline, 6 months, and 12 months.

Cognitive screening is relevant to the study’s focus because the registry’s background describes cognitive impairment as a concern in symptomatic carotid occlusion. A standardized score can provide a consistent way to assess cognitive performance at multiple visits. It is a screening measure, however, and the registry description does not establish that a score alone diagnoses a specific condition or captures every aspect of cognition.

The outcome is specified as a mean with standard deviation. A mean describes the group’s average score or change; a standard deviation describes the spread of individual measurements around that average. The primary-outcome population is participants with data collected at both timepoints for each comparison. The record does not identify the precise pair of timepoints used for each comparison, report the outcome values, or state the statistical test used to compare changes.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The outcome is continuous: MoCA is recorded as a score on a scale, and the registry specifies a mean and standard deviation. In general, a mean summarizes the center of a set of scores, while a standard deviation describes how dispersed individual scores are around that center. These quantities answer different questions. A mean change describes average change; a standard deviation does not, by itself, tell how precisely that mean has been estimated. Precision is commonly conveyed with a standard error or confidence interval, but neither is reported for the primary endpoint in the registry record.

The assessment schedule includes baseline, 6 months, and 12 months. Because measurements are collected repeatedly on participants, observations from the same person are related rather than independent. In general, an analysis of within-person change should account for that pairing or repeated-measure structure. The registry defines the primary-outcome population as participants with data at both timepoints for each comparison, which is consistent with requiring paired measurements for a change comparison. The statistical method used to calculate or compare changes is not reported in the registry record.

The record does not specify whether the primary analysis compares change from baseline at each follow-up, models scores across all visits, or uses another approach. These choices can target different quantities and may use the repeated measurements differently. An analysis based only on participants with complete measurements can also yield a result that applies most directly to those with observed data, particularly if missingness is related to participants’ outcomes or characteristics. The number missing, the reasons for missingness, and any method for addressing missing data are not reported in the registry record.

Randomization is intended, in general, to make treatment groups comparable on average at assignment, reducing confounding in a randomized contrast. This does not remove the need to describe who was randomized, who was analyzed, or how missing observations were handled. This study also includes a non-randomized observational arm, eligible for best medical management only. Comparisons involving that arm do not have the same protection against confounding as a randomized comparison. The registry record does not report whether or how the observational participants were included in primary analyses.

Confidence intervals are a general tool for expressing statistical uncertainty around an estimate. A narrower interval indicates greater precision under the method’s assumptions; an interval spanning values on both sides of no difference may indicate that the data are compatible with effects in more than one direction. Such interpretation depends on the defined contrast and analysis. No confidence intervals or primary-outcome estimates are reported in the registry record, so there is no study-specific interval to interpret.

Multiplicity arises when more than one outcome, comparison, timepoint, or analysis is examined. In general, evaluating many contrasts can increase the chance of finding an apparently notable result by chance if no suitable strategy is used. The registry identifies 9 outcome measures and three MoCA assessment times, but does not report a multiplicity strategy or specify which comparisons were designated for formal testing. It would therefore be inappropriate to assume that an adjustment was or was not performed.

The registry’s sample-size assumptions describe planning illustrations based on the observed effect, rather than the trial’s own design justification. They specify a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation, with the effect to detect set as a stated fraction of the observed effect. For time-to-event calculations, the stated output is a total number of events using Schoenfeld; other calculations give participants per arm. These are planning illustrations, not observed power. The registry does not report its own sample-size justification. Numerical planning outputs and the observed primary effect are not reported in the registry record.

Finally, a p-value, if available, would assess how unusual data at least as inconsistent with a specified null hypothesis would be under the test assumptions. It would not measure the probability that a treatment works, the probability that the null hypothesis is true, or the clinical importance of an effect. Since no primary-outcome analyses are listed, the registry record supplies no study-specific p-value to interpret. The identity of the masked party, the statistical analysis plan, interim analyses, and any analysis adjustments are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The study lists 9 outcome measures, including the primary MoCA outcome and secondary outcomes related to stroke within 30 days post procedure, intracranial hemorrhage within 72 hours post procedure, and deaths. The MoCA schedule includes baseline, 6 months, and 12 months. Multiple outcomes and timepoint comparisons can create multiplicity: in general, the more analyses considered, the greater the opportunity for chance findings if results are selected or interpreted without an appropriate plan. The registry record does not report a multiplicity strategy, identify a hierarchy among analyses, or state which timepoint contrasts were intended for formal testing.

The registry lists 0 analyses. This means that inferential results and methods for the outcomes are not reported in the registry record. It does not establish whether analyses were conducted outside the registry. A statistical analysis plan, interim analyses, and any adjustments for multiple testing are not reported in the registry record.

The primary-outcome population includes participants with data collected at both timepoints for each comparison. This definition indicates that paired data are required, but it does not describe the number of participants with missing visits or why data may be missing. The registry record does not report a missing-data method, whether all randomized participants were included in an analysis population, or whether analyses followed assignment regardless of treatment received. These omissions limit assessment of selection into the analyzed sample and the applicability of any estimate to all enrolled participants. No assumptions about the missingness pattern or analytic population should be inferred.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: colon re-section (16.7%), lung mass (16.7%), mechanical fall and facial t (16.7%), syncopal fall (16.7%), acute blood loss anemia (8.3%).

The registry’s safety figures give the number at risk and the number affected for each listed arm. For serious adverse events, the Endovascular Arm reports 12 at risk and 6 affected; the Medical Arm reports 13 at risk and 6 affected; and the Observational Arm reports 6 at risk and 3 affected. For other adverse events, the corresponding figures are 12 at risk and 10 affected, 13 at risk and 8 affected, and 6 at risk and 4 affected. The registry also lists 1 death in the Endovascular Arm, 1 in the Medical Arm, and 0 in the Observational Arm.

These are arm-level counts, not descriptions of the severity, timing, cause, or relationship to treatment for each individual event. The record lists serious adverse-event terms including Colon Re-section, Lung mass, Mechanical Fall and Facial T, and Syncopal Fall at 16.7% each, and Acute blood loss anemia and Acute respiratory failure at 8.3% each. It does not provide enough information in these figures to determine whether a person experienced more than one event or how the listed terms relate to the affected-participant counts. The safety results do not by themselves establish a comparative safety effect.

12. What the Result Does, and Does Not, Mean

The registry record documents a completed randomized phase 2 study with an endovascular arm and a medical-management arm, as well as a separate non-randomized observational arm. It identifies change in MoCA score as the primary endpoint and specifies assessments at baseline, 6 months, and 12 months. These details describe the study question and outcome framework, but they are not results.

Primary-outcome values and statistical analyses are not reported in the registry record. Therefore, it is not possible to determine from this record whether scores changed, whether changes differed across randomized groups, or how precisely any difference was estimated. The record does not support a conclusion about benefit, lack of benefit, or the clinical importance of an effect. It also does not report whether the study’s stated go/no-go criteria for a possible phase 3 study were met.

The arm-level adverse-event counts and death counts are descriptive safety information. They should be read with the study’s limited enrollment and the absence of detail about event timing, attribution, and participant-level overlap in mind. The non-randomized observational arm is not directly interchangeable with the randomized arms for causal comparisons.

In general, a study’s design and endpoint can clarify what it aimed to estimate, while estimates and their uncertainty are needed to assess what the observed data indicate. Here, the registry record provides the former but not the primary outcome results or inferential analyses. Sample-size calculations are planning illustrations, not evidence of observed power or a substitute for outcome estimates. The meaning of this trial’s cognitive and safety findings cannot be established from the posted registry information alone.

13. Why This Trial Matters Statistically

This study is statistically notable for combining a randomized comparison with a separately described non-randomized observational arm. That distinction is essential when interpreting group contrasts: randomization supports a causal comparison under suitable conduct and analysis, whereas an observational comparison may reflect differences between participants beyond the assigned management. The registry states that the observational arm was eligible for best medical management only and was not randomized.

The primary outcome is a repeated cognitive measure, with MoCA assessments at baseline, 6 months, and 12 months. Repeated measures can describe change over time, but they require a clear definition of the contrast and an analytic approach that accounts for within-person dependence. The registry record does not specify the selected contrasts or method, and it does not report outcome estimates. Thus, the design identifies an important statistical question while leaving its answer unreported in the registry record.

The record also illustrates why completed status and outcome reporting are distinct. The study is marked completed, yet 0 analyses are listed and the primary results are not reported in the registry record. Without estimates, uncertainty intervals, and clear analysis populations, readers cannot assess precision, missing-data effects, or the strength of evidence for group differences.

Finally, the exploratory phase 2 framing places emphasis on generating data for possible future study decisions. The stated planning illustrations are based on observed effects and specified assumptions, but they are not the trial’s own design justification and are not observed power. With no primary estimate or criteria outcomes reported, the registry record does not show how those planning considerations translated into the study’s conclusions.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main limitation for statistical interpretation is that the registry record does not report primary MoCA values, effect estimates, confidence intervals, p-values, or analysis methods. Although the study is marked completed, the record lists 0 analyses. The number of participants contributing to each primary comparison is also not reported, and total enrollment alone does not identify the size of the outcome-analysis population.

The endpoint population requires data at both timepoints for each comparison, but the record does not describe missing visits, reasons for missingness, or methods used to address incomplete measurements. It does not state whether analyses included all randomized participants or only those with complete data. The exact contrasts across baseline, 6 months, and 12 months are not reported, nor is any plan for multiplicity across the listed outcome measures.

The registry describes single masking but does not identify who was masked. It does not report allocation procedures, a full statistical analysis plan, interim analyses, or the study’s own sample-size justification. The stated sample-size calculations are planning illustrations, not a report of the design rationale or observed power.

Interpretation of the observational arm has an additional limitation: it was not randomized and was eligible for best medical management only. It should not be treated as equivalent to a randomized comparator. Finally, adverse-event counts are reported by arm, but event timing, attribution, and participant-level overlap are not described in the record. These gaps restrict assessment of both outcome validity and safety comparisons.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: NeuroCognition After Carotid Recanalization — NCT04219774.
• Registry record last updated 2025-05-09; status last verified 2025-03.
• Results first posted 2025-05-09.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

NCT04219774, titled NeuroCognition After Carotid Recanalization, is a completed phase 2, randomized, single-masked, parallel study sponsored by Duke University. Enrollment is listed as 25; the recorded start date is 2020-05-01 and primary completion date is 2024-03-14.

The randomized arms are endovascular intervention and best medical management, with aspirin and clopidogrel named in the intervention listing. A non-randomized observational arm is also described. The primary outcome is change in MoCA score at baseline, 6 months, and 12 months, with a mean and standard deviation specified. The primary-outcome population is participants with data at both timepoints for each comparison.

The registry lists 9 outcome measures and 0 analyses. Primary-outcome estimates and analysis methods are not reported in the registry record. Safety counts are reported for serious and other adverse events and deaths across the three arms.